Patients would no longer have to wake up in the middle of the night to take their pills, Purdue told doctors. One OxyContin tablet in the morning and one before bed would provide "smooth and sustained pain control all day and all night."

When Purdue unveiled OxyContin in 1996, it touted 12-hour duration.

On the strength of that promise, OxyContin became America's bestselling painkiller, and Purdue reaped $31 billion in revenue.

But OxyContin's stunning success masked a fundamental problem: The drug wears off hours early in many people, a Los Angeles Times investigation found. OxyContin is a chemical cousin of heroin, and when it doesn't last, patients can experience excruciating symptoms of withdrawal, including an intense craving for the drug.

The problem offers new insight into why so many people have become addicted to OxyContin, one of the most abused pharmaceuticals in U.S. history.

Over the last 20 years, more than 7 million Americans have abused OxyContin, according to the federal government's National Survey on Drug Use and Health. The drug is widely blamed for setting off the nation's prescription opioid epidemic, which has claimed more than 190,000 lives from overdoses involving OxyContin and other painkillers since 1999.

The internal Purdue documents reviewed by The Times come from court cases and government investigations and include many records sealed by the courts. They span three decades, from the conception of OxyContin in the mid-1980s to 2011, and include emails, memos, meeting minutes and sales reports, as well as sworn testimony by executives, sales reps and other employees.

The documents provide a detailed picture of the development and marketing of OxyContin, how Purdue executives responded to complaints that its effects wear off early, and their fears about the financial impact of any departure from 12-hour dosing.

Experts said that when there are gaps in the effect of a narcotic like OxyContin, patients can suffer body aches, nausea, anxiety and other symptoms of withdrawal. When the agony is relieved by the next dose, it creates a cycle of pain and euphoria that fosters addiction, they said.

OxyContin taken at 12-hour intervals could be "the perfect recipe for addiction," said Theodore J. Cicero, a neuropharmacologist at the Washington University School of Medicine in St. Louis and a leading researcher on how opioids affect the brain.

Patients in whom the drug doesn't last 12 hours can suffer both a return of their underlying pain and "the beginning stages of acute withdrawal," Cicero said. "That becomes a very powerful motivator for people to take more drugs."

Related Stories

Pain-pill giant Purdue Pharma LP will stop promoting its opioid drugs to doctors, a retreat after years of criticism that the company's aggressive sales efforts helped lay the foundation of the U.S. addiction crisis.

The company told employees this week that it would cut its sales force by more than half, to 200 workers. It plans to send a letter Monday to doctors saying that its salespeople will no longer come to their clinics to talk about the company's pain products.

"We have restructured and significantly reduced our commercial operation and will no longer be promoting opioids to prescribers," the company said in a statement. Instead, any questions doctors have will be directed to the Stamford, Connecticut-based company's medical affairs department.

OxyContin, approved in 1995, is the closely held company's biggest-selling drug, though sales of the pain pill have declined in recent years amid competition from generics. It generated $1.8 billion in 2017, down from $2.8 billion five years earlier, according to data compiled by Symphony Health Solutions. It also sells the painkiller Hysingla.

After three defendants fatally overdosed in a single week last year, it became clear that Buffalo's ordinary drug treatment court was no match for the heroin and painkiller crisis.

Now the city is experimenting with the nation's first opioid crisis intervention court, which can get users into treatment within hours of their arrest instead of days, requires them to check in with a judge every day for a month instead of once a week, and puts them on strict curfews. Administering justice takes a back seat to the overarching goal of simply keeping defendants alive.

[...] Buffalo-area health officials blamed 300 deaths on opioid overdoses in 2016, up from 127 two years earlier. That includes a young couple who did not make it to their second drug court appearance last spring. The woman's father arrived instead to tell the judge his daughter and her boyfriend had died the night before.

[...] "This 30-day thing is like being beat up and being asked to get in the ring again, and you're required to," 36-year-old Ron Woods said after one of his daily face-to-face meetings with City Court Judge Craig Hannah, who presides over the program.

Woods said his heroin use started with an addiction to painkillers prescribed after cancer treatments that began when he was 21. He was arrested on drug charges in mid-May and agreed to intervention with the dual hope of kicking the opioids that have killed two dozen friends and seeing the felony charges against him reduced or dismissed.

[...] "I don't want to die in the streets, especially with the fentanyl out there," Sammy Delgado, one of the handcuffed defendants, said.

Following hundreds of lawsuits over the years against pharmaceutical giant Purdue Pharma, Colorado's attorney general is suing the OxyContin creator for its "significant role in causing the opioid epidemic." The lawsuit claims Purdue Pharma L.P. and Purdue Pharma Inc. deluded doctors and patients in Colorado about the potential for addiction with prescription opioids and continued to push the drugs. And it comes amid news that the company's former chairman and president, Richard Sackler, has patented a new drug to help wean addicts from opioids.

[...] In federal court in 2007, three top current and former employees for Purdue pleaded guilty to criminal charges, admitting that they had falsely led doctors and their patients to believe that OxyContin was less likely to be abused than other drugs in its class, according to The New York Times. Then earlier this year, the Wall Street Journal reported that Purdue planned to stop promoting the drug.

Now, it seems, a new business venture is only adding to the outcry. The Financial Times reported that Sackler, whose family owns Purdue Pharma, a multibillion-dollar company, patented a new drug earlier this year that is a form of buprenorphine, a mild opioid that is used to ease withdrawal symptoms. However, some are expressing outrage that the Sacklers, who have in essence profited from opioid addictions, may soon be profiting from the antidote. "It's reprehensible what Purdue Pharma has done to our public health," Luke Nasta, director of Camelot, a New York-based treatment center for drug and alcohol addiction, told the Financial Times. He told the newspaper that the Sackler family "shouldn't be allowed to peddle any more synthetic opiates - and that includes opioid substitutes."

Financial Times also reported that the Sackler family owns Rhodes Pharma, "a little-known Rhode Island-based drugmaker that is among the largest producers of off-patent generic opioids in the U.S."

"In particular, he finishes by noting that people with chronic or terminal illness expect continued prescriptions of opioid painkillers and therefore an outright ban is problematic."

I have stage 4 PCa, with bone mets all over the place. It hurts. A lot. I take Tramadol when necessary, but only in extremis because most terminal cancer patients know what's coming near the end. It's best to keep the tolerance down so it still works when I really need. Addiction is kind of meaningless when your life expectancy is short. That said, Tramadol is considered low-risk in terms of addiction compared to oxycodone and hydrocodone.

What John Doucheiver doesn't seem to get is that late-stage cancer treatment is almost exclusively palliative. i.e.pain management. That means pain killers. Strong ones.

I hope the son of bitch gets a big fat adenocarcinoma in his colon. It would, by proximity, metastacize to his head.

"Addiction is kind of meaningless when your life expectancy is short."

Exactly. If a person has high blood pressure, and his blood pressure pills enable him to continue living, then he is "addicted" to those pills. Withdrawal symptoms include - death.

So, another person has a condition which causes him severe pain. Pain pills enable him to function normally, or close to normally. Without the pills, he cannot function. It's really that simple, he has to have the pain medication. He is, by definition, "addicted". Just like any drug addled criminal in the back alleys, he can't face life without his drugs. Purdue pulled the wool over the nation's eyes, by changing the definition of "addiction". Supposedly, a terminally ill patient cannot be an addict - BUT HE IS!!

AC above has justification for being addicted to his pills. It's not an illicit thing, he suffers, and he needs his pain pills to function. But, he's an addict.

An outright ban of any drug is going to be counterproductive. The least used drugs in the world have their uses, or they wouldn't exist. The most used drugs are being abused, to be sure, but they came to exist because there are legitimate uses for them.

There should be a ban, though. The pharmaceuticals should be banned from advertising their wares on television, radio, and the internet. The latest thing I'm hearing, is for EPI - some kind of digestive disorder. In the commercial, people are urged to discuss the problem with their doctors, and to name the specific EPI treatment specifically. Like - doctors have never heard of digestive disorders before, and they'll only learn of them if the patient teaches the doctor about them.

Ban big pharma from advertising, and a lot of our addiction problems will start curing themselves. Take doctors back about two or three decades, when they were reluctant to prescribe opioids, but they would do so with justification. Of course we need opioids, but you don't pass them out like candy to every person who stubs his toe, or whacks his thumb with a hammer. Fek, that's stupid.

And, oh yeah. "I hope the son of bitch gets a big fat adenocarcinoma in his colon. It would, by proximity, metastacize to his head." Thumbs up for that one!! 👍

Yes a lot of people are in search of a problem that can explain X. Really a result of people having too much fucking time on their hands, and not enough productive work to do.

Blocking advertising may keep these people from going: "Oh yes! I must have OCBPSTFF as this add suggests, and this magical pill can cure it!". But stopping these types of advertisments might not work as well in the US because of corruption at every level.

The doctors are pushing this shit. So I guess people would have to avoid going to the doctor all together!

"Oh you indicated on the questionnaire you are experiencing low-to-moderate, intermittent, back-ache. Have you heard of Heroin-Lite (TM)?"

Anyone using the word "problematic" gives themselves away as a clueless fuck-wit on the given subject. It basically means he will virtue-grand-stand about current policy but has no better solutions. A total fucking tool, and a waste of time to listen to.

Utilizing the word "problematic" is not nearly as bad as an idiot who would utilize the word "utilize" and its variants. Whenever one would write "utilize", one should write "use" instead because the word "utilize" is problematic.

--ALL LIABILITY IS EXPRESSLY DISCLAIMED FOR PERSONAL INJURY OR DEATH THAT RESULTS FROM READING THE SOURCE CODE.

My arthritis specialist had me try Tramadol in 2010. And he said to take it every day. I quickly realized it didn't like it. I quit taking it because:* I didn't like the side effects (jittery, causes restless leg, and even one time an auditory hallucination)* I couldn't easily stop and start taking it at will -- because it has withdrawal symptoms that I liked even less* I found it to be way too addictive for me

So I quit taking it completely. I hated it. I had already been taking hydrocodone, occasionally, as needed, for years, and still do to this day. I could sometimes even take quite a bit if needed. But I never had any bad side effects. No withdrawal -- that I am aware of. As far as I know, I don't have a tolerance, because I just don't take it very often. I like to start with 1/2 tablet and work up from there. I can stop it, and start it as I please, unlike Tramadol.

When my primary care doctor asked what the auditory hallucination was like, I told her that in the middle of the night I could hear what sounded like voices outside my house talking. She asked what did they say? They didn't say anything intelligible. When I would listen to hear, there was nothing. When I would stop listening for it, and think about something else, I could hear a low background sound of voices again, but nothing intelligible. And again, when I would listen more closely -- nothing. That was definitely when I quit taking Tramadol after about four months in 2010.

--ALL LIABILITY IS EXPRESSLY DISCLAIMED FOR PERSONAL INJURY OR DEATH THAT RESULTS FROM READING THE SOURCE CODE.

John Oliver may be a smug douchebag in the general case but my paraphrasing of his summary may also be at fault. I found his explanation to be concise and his summary to be nuanced and even. He has some cheap, tasteless jokes but you'll find that common to every topic he covers.

Regarding protate cancer spreading to bones, an ex-housemate died of a similiar condition in 2015. Yes, it hurts. It hurts in every bone. Facing that without painkillers would be horrendous and I fully understand why people consider suicide in such circumstances.

What undermines the case for very strong painkillers is people, like me, who get prescribed morphine variants for wrist injuries and suchlike. The medication doesn't work selectively and therefore all niggling sources of pain are blocked. You feel young and fitting fit. Unfortunately, this starts a cycle of addiction which has little difference to cocaine addiction or heroin addiction - with the exception that a medically qualified doctor is the drug pusher.

Someone very close to me lost a similar battle last September. She was taking only Tramadol and nortriptyline until the last week of her life, at which point she was in hospital and had a syringe driver administering morphine. In the UK, when a patient has that kind of diagnosis then medical professionals pretty much stop worrying about addiction - it's a nonsensical concern given the prognosis - but they do have to keep the issue of acclimatisation in mind to a certain degree for the reasons you mention. The last two days of her life are my recurring nightmare such that not dreaming is a blessing. To see someone who was so independent, so clever and so witty have all that stripped from them by both disease and treatment has ensured that if I'm ever given a similar diagnosis, I'm heading straight to the nearest drug dealer to buy enough heroin to kill me in one hit.

But the government says that sweet Jane is causing the opioid crisis! And government wouldn't ever lie! If only we doubled down and put anyone in jail who's ever advocated for medical weed (bunch of pot heads anyway, just want an excuse to get high), nobody would be abusing opioids!

There are a lot of details give, about how the drugs are pushed. I stumbled over that while searching for that infamous statement that "less than 1% of pain killer prescriptions result in addiction". Which, of course, was utter bullshit.

Indeed. I'm often shocked at how Mercola's site links are often near the top of any internet search on a medical topic. Mainstream medicine and Big Pharma have had their share of scandals over the years, but Mercola seems to seek out every form of quackery there is and put his personal stamp of approval on it.

He actively encourages people to ignore a lot of mainstream medical advice. Aside from being an anti-vaxxer (which itself is likely to lead to a lot more serious childhood illnesses, serious complications, and deaths in the coming years), he's an AIDS denialist, he encourages people on prescription medication to stop taking them (even if they have serious conditions), he is anti-sunscreen (well, unless you use his questionable "natural" stuff like "green tea" that he'll sell you) even though skin cancer is becoming a more serious problem... meanwhile hawking his own tanning beds! The guy has even gone so far as to promote his own bizarre BS "thermal" testing as a safer alternative to mammograms for breast cancer screening, or to claim that cancer is merely a "fungus" that can be cured with baking soda. (I wish I were making this stuff up.) The dude is even an eyeglasses denialist [mercola.com]!

And this is aside from all of his anti-science propaganda and promotion of conspiracy theories. The guy is a public menace. I have absolutely no doubt that thousands of people every year suffer serious ill effects if not life-threatening or fatal ones due to following his advice.

I have absolutely no doubt that thousands of people every year suffer serious ill effects if not life-threatening or fatal ones due to following his advice

Well, I've never read that site, but how does it compare to just medical errors:

Their analysis, published in the BMJ on Tuesday, shows that “medical errors” in hospitals and other health-care facilities are incredibly common and may now be the third-leading cause of death in the United States — claiming 251,000 lives every year, more than respiratory disease, accidents, stroke and Alzheimer’s.

The thing is that just doing nothing (or placebo) is often the best choice when it comes to medical treatment. Our understanding is extremely rudimentary (can you pick one precise prediction that came true on the topic in the last ten years?), and it is easier to break things you don't understand that fix them. Further there is no current incentive to improve on this since researchers in that area are continuing to get away with doing NHST and p hacking instead of science.

This guys ideas seem less dangerous than a bunch of deeply misinformed people armed with super-concentrated chemicals who want to inject you and cut you open.

The entire medical culture is sick as hell and you should be very scared of having any interaction with them. And once again, that isn't to say any of this alternative stuff works, it is just less dangerous. Similar to how people started noticing how strong the placebo effect was during the civil war because the standard treatments like bloodletting were killing patients. And think about the mountain of details they argued about back then too (how much to bleed from where, the mechanism of action, etc). It would have been unbelievable if that was all based on nothing and doing more harm than good wouldn't it?

This study that claims 251,454 patients die each year is here [west-info.eu].

Before citing it as strong evidence, you should note that that estimate of 250,000 deaths is based on data from three papers that collectively accounted for 35 "preventable" deaths. No, that's not a typo. That's quite an extrapolation.

The gist is that "study" got a lot of press, but it's probably off by at least an order of magnitude or so. (It's also difficult to determine after the fact how many deaths were actually "preventable" given what was known by clinicians at the time.) None of this should excuse medical errors -- and "only" 20,000ish deaths/year is WAY too much.

This guys ideas seem less dangerous than a bunch of deeply misinformed people armed with super-concentrated chemicals who want to inject you and cut you open.

First off, we're talking about one guy with a huge amount of influence. Is it possible that there's SOME other medical doctor out there who actually gives out bad advice that likely results in serious side effects if not deaths in a large number of patients? Maybe -- but I doubt he'd stay a doctor very long. A combination of malpractice suits would likely drive him from the profession, if he wasn't fired or had his license revoked first. It seems most serious medical errors that result in deaths occur during hospital care. Mercola isn't dealing with that: he's advising people to avoid ALL scientifically-proven preventative medicine for many illnesses.

Errors are just that: errors. They are lapses in judgment or whatever. Reasonable physicians with better knowledge and further analysis of the situation can identify what actually went wrong. By the way, you know how such studies KNOW something went wrong? SCIENCE. We look at causality and say, "Huh -- this guy had a tumor, and we didn't cut it out, so he died. Maybe we should cut it out in future patients." Mercola just says, "Oh, it's a fungus! Rub some baking soda on it!" No rigorous analysis. No statistical evidence of effectiveness. Just hokum and quackery.

Making accidental errors that you later can identify as errors is quite different from deliberately promoting stuff that is KNOWN to be false, stuff that contradicts established science, continuing to promote such stuff after you've been definitively disproven, etc.

Car analogy: If I sell you a car that had poor maintenance on the brake system, and you have an accident and die, I made an error. Depending on the situation, I may or may not be legally culpable for negligence. If, on the other hand, I sell you a car with the brake system removed and claim "If you just take these vitamin pills, you can stop your car with the power of your thoughts" and you have an accident and die, I should be rightly called out as a quack deliberately peddling unsafe cars and ridiculous advice.

Before citing it as strong evidence, you should note that that estimate of 250,000 deaths is based on data from three papers that collectively accounted for 35 "preventable" deaths. No, that's not a typo. That's quite an extrapolation.

I went to table 1 and checked the first reference in that table (ref 11). It looks like that one alone dealt with >10,000x more records than you claim:

Of the total of 323,993 deaths among patients who experienced one or more PSIs from 2000 through 2002, 263,864, or 81%, of these deaths were potentially attributable to the patient safety incident(s)

On the other hand I haven't checked this paper in detail, it is quite possible it will end up being normal medical research quality (extremely crappy). But getting such an estimate does not seem like it would be problematic in principle (besides the trouble with defining "error"). So that will be the fault of NIH, CDC, etc for not funding studies to collect this important info.

I'm not normally responding to ACs these days, but I need to correct an error here. If you actually read the study in the link you provided (rather than merely its "summary"), you'll find the following statement on page 6:

We determined that the 16 PSIs we studied may have contributed to 263,864 deaths in the Medicare population from 2000 through 2002. Eighty-one percent of these preventable deaths were potentially attributable to the patient safety incident.

These "weasel words" are there for very good reasons, despite being juxtaposed with seemingly contradictory rhetoric like "these preventable deaths."

Those "263,864 deaths" quoted in the meta-study were extrapolated from analysis of "16 PSIs," which stands for "patient safety indicator." In other words, they didn't actually examine any specific cases to determine whether a "preventable death" occurred due to the details of the case. Instead, they extrapolated on the basis of vague issues that potentially indicate a problem with "patient safety." Some of those "indicators" seem clearer than others (see Appendix A for the list). For example, "foreign body left during procedure" sounds like a clear medical error, though again whether it was a primary cause of death was not investigated in any specific case in that study. On the other hand, "Post-operative hemorrhage or hematoma" -- well, lots of people experience bleeding post-op, especially if they don't adhere to doctor's instructions. Trying to extrapolate how many "preventable deaths" occurred based on an "indicator" like that seems problematic, though.

So, how did they come up with their numbers? Well, if you look at the Appendix F from your link, you'll see they extrapolated based on statistics from this study [jamanetwork.com]. Except that study didn't actually examine mortality or "preventable deaths" by examining individual cases either, but rather used a sort of "case-control" methodology to look at the difference between outcomes with patients who did and did not experience these "PSIs." On that basis, they calculated "excess mortality" likely due to those PSIs.

That may sound a little better methodologically (and I agree), but then you read their conclusion:"one can infer that the 18 types of medical injuries may add to a total of 2.4 million extra days of hospitalization, $9.3 billion excess charges, and 32 591 attributable deaths in the United States annually."

So, your linked study took the estimates of "excess mortality" and applied them to a new dataset to extrapolate possible deaths and possible medical errors that may have contributed to these deaths, and then came up with an estimate for the Medicare patients alone that is 2.7 times higher than the estimates for ALL patients in the U.S. in the study I linked (and from which they got their estimates for mortality), even though the study I linked did a much less rigorous analysis.

Anyhow, I stick to my original statement: only 35 actual cases were studied and determined to be preventable based on individual facts. I'm willing to accept a more rigorous case-control analysis or something as a way to extrapolate a broader estimate, but I don't see evidence that your linked study or the broader metastudy that's being discussed here used such methods. And given that their own source for methodology estimated the annual death rate as nearly an order of magnitude lower, I'd say there are serious red flags here.

Bottom line is the ~250k/year estimate is based on a metastudy that's based on 3 studies that looked at 35 actual preventable deaths, and based on one other study that made extrapolations based on methodology and extrapolation procedures from yet another study that came up with an estimate of ~32k/year.

Car analogy: If I sell you a car that had poor maintenance on the brake system, and you have an accident and die, I made an error. Depending on the situation, I may or may not be legally culpable for negligence. If, on the other hand, I sell you a car with the brake system removed and claim "If you just take these vitamin pills, you can stop your car with the power of your thoughts" and you have an accident and die, I should be rightly called out as a quack deliberately peddling unsafe cars and ridiculous advice.

I'd say the current situation is that the way mainstream medical research is done (and used to inform treatments) is like selling a car while having no idea whether it contains a brake system or not because you don't know what one would look like. However you did check that the car rolls to a stop eventually (null hypothesis of "no stopping" was false), so it probably has brakes.

I have been there. To the meetings, the journal clubs, etc. It is standard to have no idea what a p-value means yet use them for everything.